Background: Chronic postsurgical pain (CPSP) is common after off-pump coronary artery bypass grafting (OPCABG) in elderly patients. This trial investigated the efficacy of perioperative transcutaneous auricular vagus nerve stimulation (taVNS) and pectoral-intercostal fascial block (PIFB) for CPSP prevention. Methods: In this 2× 2 factorial trial, 260 elderly patients (≥ 60 years) undergoing OPCABG were randomized to taVNS + ropivacaine PIFB, taVNS + placebo PIFB, sham taVNS + ropivacaine PIFB, or sham taVNS + placebo PIFB groups. The primary outcome was CPSP incidence at 3 months postoperatively. Several secondary outcomes were evaluated. Logistic regression was employed to analyze risk factors associated with CPSP. Lastly, mediation analyses were performed to explore the mediating factors between interventions and CPSP. Results: The overall incidence of CPSP was 34.6%. No interaction was found between taVNS and PIFB. Compared with sham taVNS, taVNS significantly reduced CPSP incidence (28.6% vs 40.9%, P = 0.036), alleviated acute pain and improved recovery quality. PIFB did not reduce overall CPSP incidence (30.2% vs 38.8%, P = 0.143), though it alleviated acute pain on postoperative day 1 and reduced moderate-to-severe CPSP. Risk factors for CPSP included preoperative anxiety, pain catastrophizing, acute postoperative pain, and high IL-6 levels. Mediation analysis indicated taVNS’s benefits were partially mediated by reducing acute pain (19.3%) and IL-6 (20.4%). Conclusion: Perioperative taVNS significantly reduced CPSP incidence and enhanced postoperative recovery in elderly OPCABG patients, partly mediated by alleviating acute pain and inflammation. Single-shot PIFB showed limited preventive effect on overall CPSP. Keywords: postoperative pain, vagus nerve stimulation, nerve block, aged, randomized controlled trial
Cui et al. (2026) studied this question.